Wednesday, March 11, 2009

Back in 2003, I had one of those breakthrough moments, the type you associate with light bulbs switching on. I was at the American Psychiatric Association's annual meeting attending a symposium on genetics. Robert Freedman MD of the University of Colorado started explaining his research into schizophrenia.

"The DSM-IV was not designed with human gene function in mind and genes do not encode for psychopathology," he said. Instead, "genes encode simple molecules in cells that alter cell function and brain information processing."

I had kind of been aware of this, but this time I went, "Aha!"

Dr Freedman had been exploring the link between "sensory gating disturbance" and why people with schizophrenia crave nicotine. A normal person, for instance, can tune out the second of two repetitive sounds. Many people with schizophrenia, however, cannot, and so have great trouble concentrating.

It turns out that the alpha7 nicotinic receptor mediates sensory gating, and thanks to the work of Dr Freedman and others, drug manufacturers have a nicotinic agonist in development.

The upshot of my Aha! moment was the realization that to better understand my own illness (bipolar) I needed to research other illnesses as well, such as schizophrenia. The brain, after all, doesn't organize itself according to the DSM.

A couple of years ago, at the APA, I listened to various schizophrenia researchers talk about the thinking processes of the brain. To vastly oversimplify, individuals with schizophrenia have trouble tuning out distractions from competing neurons; yet what is also in play is the potential for novel neuronal alignments to generate novel thoughts.

At the same APA meeting, Nancy Andreasen MD, PhD of the University of Iowa discussed her research into creativity, which began with a hunch based on schizophrenia.

What we seem to be looking at is that fine edge where productive novel thinking ventures close to the precipice of pathologically delusional thinking. I raised this issue in an earlier blog about John Nash and in another blog about evolutionary psychiatry.

Dr Kaufman talks about "latent inhibition" (LI), the brain's ability to unconsciously filter out information. High latent inhibition is conducive to rational thought. Low latent inhibition is associated with psychosis and schizophrenia.

But can there be an upside to low latent inhibition? Writes Dr Kaufman:

"Recently researchers have wondered whether a reduced latent inhibition can actually be beneficial for creativity. After all, decreased LI may make an individual more likely to see connections that others may not notice."

In support of this, Dr Kaufman cites research by Shelley Carson PhD of Harvard showing that those with a high IQ and decreased LI reported increased creative achievement. The key here appears to be adequate levels of executive function to ride herd on the stampede of incoming information. The catch is people with schizophrenia tend to score very low on measures of executive function.

Another point that Dr Kaufman raises is that people with schizophrenia have difficulty sorting out their emotions. Again, they are overwhelmed. Here's where it gets interesting: A lot of these emotions may be intuitions that are accurate, thus enhancing the potential for making a creative connection.

Dr Kaufman is engaged in research on subjects with normal levels of executive function. This involves measuring LI. In the first part of the task, subjects need to screen out certain irrelevant input to achieve success; in the second part, processing that same irrelevant information is vital to arriving at the right answer.

According to Dr Kaufman:

"I found that those who reported a higher faith in intuition displayed decreased latent inhibition. In other words, those who reported higher faith in their intuitions allowed the information that was tagged as irrelevant in the first phase to be treated as novel and interesting in the second phase, and by doing so were faster at figuring out the answer."

Alas, it seems, those with schizophrenia lack the necessary executive function to cope. Way too much information. "Indeed," says Dr Kaufman, "this idea of 'sensory gating' has been quite influential in the literature on schizophrenia."

Sensory gating! Where have I heard that before?

Much more research is needed, Dr Kaufman acknowledges. "Nonetheless, an understanding of the biological basis of individual differences in different forms of implicit processing and their relationship to openness to experience and intuition will surely increase our understanding of how certain individuals attain the highest levels of creative accomplishment."

And in conclusion: "Perhaps such research will even allow us to stop rehashing old ideas about the potential links between madness and creativity and re-conceptualize the thought processes that are prone to psychosis not as madness at all but as potential for creative greatness."

If all that sounds way too simple, Dr Krystal rolled out a far more complicated scenario involving glutamate’s tag team partner, GABA (the main inhibitory neurotransmitter), in particular a group of GABA neurons referred to as chandelier cells. In this context, GABA helps prevent glutamate from running wild. When involved in working memory, GABA tunes out distractions from competing neurons, allowing the brain to focus. But a deficit in NMDA glutamate receptor function effectively disables GABA chandelier cells. ...

2 comments:

Cristina Romero-Sierra
said...

Hi John. I have heard that before, that people with schizophrenia and other people who experience psychosis have a lot of information racing through their minds because they have little filtering of information.

So you're saying if a person has good intuition and good execution combined with little filtering, they can be highly creative?

I've used CBT (cognitive behavioural therapy) to help my filtering (for bipolar thinking), which has decreased my tendency towards psychotic thinking tremendously. I have definitely found CBT has also increased my creativity.

My question is, do you know if CBT been found to be helpful for people with schizophrenia? And do you know if CBT has been found to increase creativity?

Hi, Cristina. Very interesting questions. I need to emphasize that any opinions in this area - even expert opinion - is highly speculative. The research is fascinating, but we're nowhere near close to definitive answers yet. So less filtering and good intuition combined with adequate executive function leading to high creativity is at best an inspired guess. Nevertheless, it seems like researchers are are using this assumption as a good starting point. And for me it ties together a lot of loose ends - so I'm going to be watching this very closely to see where it leads.

Off the top of my head, CBT hasn't been found helpful for schizophrenia - but I would qualify that. Clearly, you have experienced CBT reducing your tendency toward psychosis. But people with schizophrenia have more going on besides just psychosis. Namely a lot of cognitive dysfunction. So if they are at the low end of dysfunction, success is problematic. I'm just guessing - but I'm sure CBT would work for those whose have fewer problems with cognitive function. Never say never. Never give up hope. But this is a population a lot harder to work with.

I haven't heard about CBT increasing creativity. But CBT is all about being in charge of our brains. My guess is our cognitive skills can help us stay in the "creative zone."But I highly doubt CBT or anything else can take a non-creative person and turn them creative.

But, again, I'm just guessing, and so is everyone else. But please feel free to post your best guesses, too.